tracking progression we can better manage our patients. Like any tool, any instrument you ve got to

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1 EIYESS ALBEINUTI, MD 1 As we know OCT has become very instrumental in taking care of glaucoma patients whether we have the ability to objectively image the RNFL and therefore pickup earlier signs of damage and by tracking progression we can better manage our patients. Like any tool, any instrument you ve got to know how to use it, you ve got to make sure the information you get from it is accurate and you have to know what kind of, you have to make proper decisions using that. What I m going to do is use the Zeiss HD-OCT as the backdrop. The different SD-OCT machines are pretty similar in what they can offer but I m familiar with the Zeiss so I ll use that just to review some principles. Some of them apply to that machine only the Cirrus where as others can be generalizable. So I m going to just review some of the highlights of the RNFL and optic nerve head analysis. We ve discussed some of the factors that limit reliability and we re going to offer just some clinical pearls about interpreting OCT and applying it clinically. So you guys have heard the SD-OCT is a significant improvement over the time domain OCT, it can take more scans, it can give you more information faster, it has better resolution, but practically speaking the advantage here is that you have an optic, you have 3D information. You have a bigger area that you can look at the RNFL instead of just a simple circular peripapillary area. In this case the circumpapillary scan is actually extracted from this cube, this optic disc cube of multiple B scans. It also can identify the optic nerve head automatically so there s, it s user independent from

2 EIYESS ALBEINUTI, MD 2 that standpoint. And there s also as we discussed, there s an SLO built in so you can actually see the area that you re scanning and you can make sure that you have a good image. So here s the typical printout and when you re looking at a patient who s a glaucoma suspect and you see one of these printouts the basic question you re always trying to answer is does this patient have glaucoma. And to answer that question you have to answer 2 other ones, and first is are the results accurate, is this a good test. And secondly, is it abnormal. So in dealing with the first part, the first thing that I try to make sure is that you have a good signal strength. You have to have above 6 for it to be acceptable and you know the higher the better. You also you know having a good signal strength improves reliability, decreases the variability and a lower signal strength can tend to get lower measurements with the RNFL. Factors that can affect that generally speaking media opacity, corneal surface irregularities, and sometimes it s the machine itself, if it s smudged or there s some sort of issue with that. Although you don t have to dilate pupils you can get through a 2mm pupil in some cases it does help to dilate pupils to get around focal opacities, using artificial tears before testing is useful, sometimes you just got to go to cataract surgery if you re having trouble. And if for some reason you re not getting good signal strengths on a regular basis and you ve ruled out some of these other causes you may want to have the instrument serviced. But signal strength is very important.

3 EIYESS ALBEINUTI, MD 3 So once I ve verified a good signal strength, the next thing to do is to just take a look at the RNFL thickness map and that s that color coded map right in the middle there. And you know the OCT can give you a lot of different analysis, can do a lot of things for you but fundamentally what it s doing, it s measuring the nerve fiber layer and that s what this thickness map shows you. It visually demonstrates what is you know hard to appreciate clinically. Although you can assess for nerve fiber layer just on funduscopic examination you re not going to be able to measure it and really visualize it like you can in this case. So the first thing I do is take a look at that map and there s just a wealth of information right in that color coded map. So I ll look at the distribution of the nerve fiber layer, I ll see kind of the pattern that you see you like to see that orange and yellow especially superior and inferior. I tend to check for any signs of wedge defects which you might pick up as these wedge like areas that appear thin. And then on the deviation map below that you can correlate the nerve fiber layer with the pattern, the vasculature, the general rule is that the major nerve fiber layer areas of thickness are the major bundles follow the nerve-or follow the pattern of the vessels. So here are some examples. You have at the top some normal optic nerves and you see a nice beautiful pattern. And then down below on the left that right eye shows a pretty clear inferonasal, I m sorry inferotemporal wedge defect that you can see on the map and the deviation map basically compares this information to your normative database and with yellow and red it can highlight areas

4 EIYESS ALBEINUTI, MD 4 of excessive thinness compared to the normal database set at the 5 th and 1 st percentiles. So this is a clear example of nerve fiber layer defect in the right eye. In the left eye overall things look pretty good there with the nerve fiber layer, although maybe temporally there could be a suggestion of some sort of defect close to fixation, but it s not clear. As for the picture on the right you see that there is a little bit more diffuse thinness to the nerve fiber layer, you see more yellow as opposed to red and orange so that could be a sign of glaucoma. And then on the right optic nerve inferotemporally there may be, there s a suggestion there of a wedge defect on the map. Although you look at the deviation map and it doesn t really show up as being particularly abnormal. So speaking of deviation maps in addition to identifying areas of excessive thinness compared to normals, I like to look at that to make sure I have a good scan. So there first thing is to make sure there s no major fixation losses and those you can identify by breaks in the vessels. So the scans are taken as sequential B scans from top to bottom and if you notice that there s a break in the pattern that s a sign of fixation. If it s really small like towards the top on the left and it s peripheral, it s not a big deal. But something that s central and closer something that involves the circular scan, that can affect your measurements quite a bit. Also you can check for any PVDs, Weiss rings, the one in the middle on the left happens to be just inside the circle so probably is not going to affect things much, but the other one crosses the circular scan and that s going to distort your findings.

5 EIYESS ALBEINUTI, MD 5 And then lastly you want to make sure the centration is good. Now with this instrument centration is automated and it s very uncommon to have an abnormality in the placement. There s a pretty good reliable algorithm that can identify where the disc is and center the scan appropriately which is important for repeatability. Whereas the Stratus it was user dependent and they had to center the scan and so there can potentially be some issues with that. If a scan is decentered you re going to get major changes in the nerve fiber layer measurement at least in the distribution. So if it s closer towards the disc one of the sides are closer to the disc you can get an increase in the thickness there compared to the opposite side. And there s some other artifacts and algorithms, algorithm failures that can happen. That takes us to the next part of the standard printout and that s the just an image of the extracted tomograms so you can see cross sectional images through the optic nerve and the peripapillary RNFL, you have horizontal and vertical ones as well as the extracted circular tomogram. Those are worth looking at because the data that you re getting for example for your circumpapillary scan comes from how the instrument identifies the layers, the interior and posterior boundaries of the RNFL. We saw earlier today how if those tracings are not in the right spot, you re going to get wrong measurements. So the 2 sources of algorithm failures are either those tracings are not set up properly, if there s another optical interface that s confusing the machine, or if somehow these tomograms can t fit on the scan, on the window scan or the scan window.

6 EIYESS ALBEINUTI, MD 6 So here is an example of a fairly normal looking right optic nerve with pretty good pattern however just temporal there s an area of black and it seems to correlate with what seems to be a thinning of the RNFL. But if you look at the circular tomogram you ll see that that temporal area those 2 tracings converge rather than bordering around the RNFL, they actually converge onto this hyaloid, the posterior hyaloid so you get an artifact. And if you look at the macular OCT in this case you see that there is vitreomacular traction or at least adhesions with the epiretinal membrane. And in terms of not having the image within the window of the scan window, this is actually more common on the left side you see what is actually a normal optic disc you see areas of black towards the top and nasally and those areas of black they can, they actually encroach upon the circle and so you know that that s going to affect your measurement on the circumpapillary scan. And so what you end up showing is a superior nasal defect. But if you look towards the bottom you ll see that that scan is not centered properly and this is something that can be fixed before you do the scan and hopefully the technicians are well aware of ways to do that and ensure that. But there s a button that does this for the most part automatically for you, you optimize it and it should center things and enhance your image. On the right side is the more common case where we see patients with high myopia, they very typically have these nasal ring like defects where you just can t visualize the RNFL and that s because the nerve fiber layer, the nerve fiber layer just can t be, it doesn t show up on the window.

7 EIYESS ALBEINUTI, MD 7 So if you look at your horizontal scan the nasal side of that RNFL just gets close towards the edge of the window and in some cases it s more extreme. However, it s important to realize that the rest of the scan is actually pretty good so even if you can t you know it looks like it might seem like a mess at first if you can do multiple scans over time and have it centered properly you can still look at the nerve fiber layer elsewhere and be able to tell if there s any signs of progression. As for the circumpapillary RNFL thickness, this is the typical information we re used to even from the Stratus that most glaucoma, most people in general focus on. It s important to realize the limits of it because it s only focusing on one area around the RNFL but generally it does give you pretty good information. It s a nice little snapshot of how the RNFL does overall. Looking at the average thickness that s something I often tend to do and you want to generally have similar measurements for both sides. You know there s one study recently that showed that a difference of about 10 microns or more may be significant because up to about 9 is within the 95% interval for variation between averages for normal eyes. Right below that there s an RNFL symmetry measure and that doesn t really come from comparing the averages directly, it compares the profiles of the right and left eyes and so you can have totally symmetric- similar averages, it could be exactly the same. But if the 2 optic nerves have different patterns in terms of the nerve fiber layer distribution or measurements you re going to get some asymmetry. And I think that that s a little bit less reliable but it s more or less a correlation factor.

8 EIYESS ALBEINUTI, MD 8 And then the familiar breakdown of the RNFL in terms of quadrants and clock hours, the studies have found that the most useful ones are inferior quadrant average and the 7 o clock hour in the right eye and 5 o clock in the left eye which is the inferotemporal region as well as just the overall averages are useful for trying to pick out abnormalities. So if you get an abnormal RNFL profile you know in a busy clinic we re often looking for little you know easy ways to tell if someone is abnormal, are they normal, do they have glaucoma or not, so we might look at some of these colors and we want something very easy. But it s worth understanding what exactly normal is for you know what abnormal is. So just a quick review of the databases; 284 patients were found to have no signs of ocular hypertension or glaucoma with a wide age range the refractions also pretty wide but you know the lower limit there is -12 and sometimes we have patients who are more. You can see the ethnic breakdown so for example only one percent in the database were Indian, so if you have Indian patients it s going to be a little bit less applicable. Analysis of these patients, these normals, found that potentially up to about 6 microns can differ in normals between ethnicities. There can also be variations between, involving axial length and disc size that can affect the RNFL measurements. So the database when you re comparing your findings, your RNFL measurements to the normal database it doesn t do it by any of these factors except the age, it breaks it down into decade. So it s important to keep that in mind.

9 EIYESS ALBEINUTI, MD 9 Another thing is variations in the anatomy and the direction that the RNFL major bundles take and as I mentioned it does seem to generally correlate with the major vessels. And one study of young Koreans, Korean males found out there was quite a bit of disparity between patients between normal patients in terms of the pathway and the angle that their major vessels take, and in some cases that resulted in abnormalities on the OCT. So towards the right there s a normal patient and you see that nasally the thickness on average is actually thicker than the 95 th percentile and there are a couple areas superotemporally where there s some abnormality. Although if you look at the thickness map overall the pattern looks to be pretty good and this is a normal patient as I have told you ahead of time. So you can obviously see there is sometimes abnormality, quote unquote abnormalities that show up simply because there s some variations in RNFL pathway. In this case you see that the major vessels are oriented more vertically as opposed to you know superotemporal and inferotemporal and you see that the major humps on the RNFL profile are more crowded than are toward the nasal side. So it s also something to pay attention to. Now the normative database when you re comparing your patients to the normal database even though it doesn t break it down into all these different factors generally speaking that should average out and it should be factored into the database. So when you re looking at your, your, your normative database profile, you know the double humped patterns you know with the green and the yellow and the red, that should take into consideration some of these variations. But if for some

10 EIYESS ALBEINUTI, MD 10 reason someone was on outlier in terms of their anatomy, an outlier in terms of their axial length, an outlier in terms of their ethnicity and they just kind of all come together that way, you re going to have potentially an abnormality when everything is normal. And on the flipside if you get a normal study that does not necessarily rule out glaucoma. We all know that glaucoma is a progressive process so if you could have a normal scan at any one time and it could be progressing. Furthermore, there s more information available than simply the circular circumpapillary scan and that s why it s fun to look at the maps, the RNFL and deviation maps. Someone could have a totally normal RNFL profile as measured on the circle scan but further out there s potentially developing RNFL defect. So if you re, that same case you ll see that over time there s signs of inferior changes on the OCT and clinically there are some signs of nasal progression, developing of a nasal, visual field test. There s also some superior changes as well. However, we just saw that last OCT, everything was quote unquote normal. I m not going to talk about progression very much, Dr. Schuman is going to get into that but just a basic this is also a very important part of the OCT printout it s important to get 2 good baselines that are very similar, very comparable and we often get an initial OCT on a patient who s a suspect, we bring him back maybe 6 months later sometimes a little bit further out and you do a second OCT and if you re going to rely on this GPA analysis to try to tell you whether there s signs of progression it s going to take those first 2 and use that as a baseline. And if there s a big difference between them in terms of time and there s potentially progression and you don t really pick that up, your future scans

11 EIYESS ALBEINUTI, MD 11 if you re going to compare them to that are going to be less reliable. You re not going to be able to with as much certainty say that there s progression. So it s important to get 2 good scans that look the same pretty early on. The last couple things I ll talk about is just the fact that the macula OCT is also relevant in glaucoma. Sometimes in this case you can possibly see a nice superior and inferior wedge like defects in the RNFL, I don t know how well that s projecting. But in cases where it isn t, in case you can t notice it you can do a macula OCT and sometimes that ll show the defect quite nicely. So the thing about the macula OCT is you can sometimes see defects and also the macula can be a confounder, if you have some thickening or thinning in the macula due to some other retinal problem that may confound the results on your RNFL measurements. So here s an OCT we looked at earlier where there s in the right eye possibly an inferotemporal early wedge on the thickness map towards the top that doesn t show up on the deviation map. If you do the macula OCT it does seem to show up pretty clear inferotemporal wedge and that correlates nicely to a superior defect on the field. And likewise here you have a patient who over time there s some increase in the RNFL and temporally on the right side you see some thickening there compared to the normal database and macula OCT shows that there s an epiretinal membrane with some progressive thickening in the macula and that s going to show up as an increase in your RNFL. So the key thing to remember here is if for some reason you had a patient with an epiretinal membrane who was having developing edema they could also have glaucoma at the same time it would be progressing and you re not going

12 EIYESS ALBEINUTI, MD 12 to pick it up on the RNFL analysis on the GPA because it might mask it or it might even show an increase. Here is a case where on the left side you see really thick RNFL and it should be pretty clear from the SLO image what s going on but otherwise you look at the fundus just out of the courtesy and you ll see that there s a big inferior hemiretinal vein blockage with macular edema so that can obviously impact your RNFL measurements quite a bit. After Avastin the same left eye now all the sudden is normal at least in terms of the macula and if you look at the GPA you ll see how much of a difference there was in the RNFL measurements, this is obviously an extreme example but there may be some subtle cases of fluctuating edema so that s important to pay attention to. And let s do one more of these here s the right eye looks like tons of edema on that right side. So macula OCT shows nothing really, so we ll repeat the OCT and it looks normal all of a sudden, and that s because this is actually an artifact that s, that you get sometimes if the image is inverted and that was discussed earlier today about getting these mirror images sometimes. So if you set up the scan properly you shouldn t get that, but if you see something funny as Dr. Puifido said always try to you know confirm why is this abnormality there. And the last thing I ll just mention is that optic nerve head parameters are also useful and they may not have been as useful in the past but now they have the potential to be increasingly useful especially in cases if the RNFL measurements can t be reliable for whatever reasons we talked

13 EIYESS ALBEINUTI, MD 13 about. You can often look at the optic nerve head and can get very good information, there is some normative database, normative data available, we are now able to track the cup to disc ratio with their GPA software, so it s very useful and some studies have found that it s just as good s the RNFL, at least on the Cirrus OCT in terms of picking up early glaucoma. So that s another thing that should be paid attention. So in summary in trying to make the most use out of SD-OCT you want to make sure the images are you understand what causes an artifact and what causes unreliability, you want to be familiar with the factors that affect RNFL thickness such as anatomic and demographic variability and confounding macular pathology. You don t want to automatically be satisfied with a normal or abnormal scan, it s never that easy. You ve always got to keep everything in perspective and you want to pay attention to progression because often that ll give you the answer. Pay attention to optic nerve head parameters, macula OCT and always, always obviously we re focusing on OCT here because of this course but you want to correlate everything with your visual field, your optic nerve head, just the whole clinical exam, because sometimes you ll get progression or abnormalities in the other tests but not in the OCT so thank you.

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